K-RAS GENE MUTATION RELATED TO HISTOLOGICAL ATYPIAS IN HUMAN COLORECTAL ADENOMAS

To investigate the relationship of oncogene analysis to morphology, we analyzed K-ras gene mutations by dot-blot hybridization with and with out consideration of histological atypias in individual colorectal ade nomas. Each of 54 colon polyps were divided into two parts after fixat ion. One part was used as a mass to assess point mutations: the remain ing portion of each polyp was paraffin-embedded, stained with hematoxy lin and eosin, and examined for point mutations related to histologica l atypias. In the first part of our study, K-ras gene mutations at cod on 12 were detected in 13 cases (24%). In the second part of our study , 12 cases had distinctly different histological atypias. From each of these 12 cases, two areas, one with higher or one with lower grade at ypia in the same polyp were excised to analyze for K-ras gene mutation . Two of these 12 cases (17%) had the mutation in different areas of t he same tumor. These two cases contained the mutation only in the area s with higher grade atypia, and only one case added information regard ing ras mutation upon microdissection when compared to the entire biop sy. These results suggest that oligonucleotide hybridization can ident ify the majority of cases containing ras mutations despite regional mo rphologic variation. Individual cases, however, may contain clonal sub populations within adenomas with different ras sequences from other re gions within the same adenoma.